Use of topical rSm29 in combination with intravenous meglumine antimoniate in the treatment of cutaneous leishmaniasis: A randomized controlled trial.

Background: Cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is associated with an inflammatory response. Granzyme (GzmB) and IL-1β play a key role in the pathology. Meglumine antimoniate (MA) is the first-choice drug for the treatment of CL, but therapy failure is observed in up to 50% of the cases.

Efficacy of intralesional meglumine antimoniate in the treatment of canine tegumentary leishmaniasis: A Randomized controlled trial.

Dogs living in areas of Leishmania (Viannia) braziliensis transmission may present canine tegumentary leishmaniasis (CTL) characterized by cutaneous or muzzle ulcers as well as asymptomatic L. braziliensis infection. It is not clear if dogs participate in the transmission chain of L.

Leishmania braziliensis causing human disease in Northeast Brazil presents loci with genotypes in long-term equilibrium.

Background: Leishmaniases are neglected tropical diseases that inflict great burden to poor areas of the globe. Intense research has aimed to identify parasite genetic signatures predictive of infection outcomes. Consistency of diagnostic tools based on these markers would greatly benefit from accurate understanding of Leishmania spp.

Blockade of TLR2 and TLR4 Attenuates Inflammatory Response and Parasite Load in Cutaneous Leishmaniasis.

Human cutaneous leishmaniasis (CL) caused by is characterized by a pronounced inflammatory response associated with ulcer development. Monocytes/macrophages, the main cells harboring parasites, are largely responsible for parasite control. Toll-like receptor (TLR) signaling leads to the transcription of inflammatory mediators, such as IL-1β and TNF during innate immune response.

Influence of Intestinal Helminth Burden on Clinical Manifestations, Therapeutic Response, and Leishmania braziliensis Load in Patients with New World Cutaneous Leishmaniasis.

Leishmania braziliensis is the most important cause of cutaneous leishmaniasis (CL) in the Americas. A Th1-type immune response is required to control Leishmania infection, but an exaggerated inflammatory response leads to the development of ulcers seen in CL. Infection with intestinal helminths has the potential to inhibit the Th1 response in a manner that depends both on the species of helminth present as well as the burden of helminthiasis.

Evaluation of the Ability of Miltefosine Associated with Topical GM-CSF in Modulating the Immune Response of Patients with Cutaneous Leishmaniasis.

Cutaneous leishmaniasis (CL) due to is associated with an exaggerated inflammatory response and tissue damage. Miltefosine is more effective than pentavalent antimony (Sb) in the treatment of CL, and here, we evaluate the ability of Sb, miltefosine, and GM-CSF administered intravenously, orally, or topically, respectively, to modify the immune response. Patients were treated with miltefosine GM-CSF, miltefosine placebo, or Sb.

A Th2-Type Response Is Associated With Exuberant Lesions in Pregnant Women Infected With Leishmania braziliensis.

Background: Cutaneous leishmaniasis (CL) is characterized by an exaggerated inflammatory response. During pregnancy there is a decreased inflammatory response, and we have shown that pregnant women with CL develop exuberant lesions.

Methods: Cytokine production by peripheral blood mononuclear cells and the frequency of cells expressing cytokines in lesions from pregnant and nonpregnant women with CL were evaluated.

Dynamics of American tegumentary leishmaniasis in a highly endemic region for Leishmania (Viannia) braziliensis infection in northeast Brazil.

Background: American Tegumentary Leishmaniasis (ATL) caused by Leishmania braziliensis is endemic in Corte de Pedra, Northeast Brazil. Most L. braziliensis infections manifest as localized cutaneous leishmaniasis (CL).

Molecular epidemiology and in vitro evidence suggest that Leishmania braziliensis strain helps determine antimony response among American tegumenary leishmaniasis patients.

Antimony is the first line drug for treating American tegumentary leishmaniasis (ATL) in Brazil. In this country, Leishmania braziliensis causes at least three distinct forms of disease: localized cutaneous (CL), mucosal (ML) and disseminated leishmaniasis (DL). All forms can be found in Corte de Pedra, Northeast Brazil.

Oral Pentoxifylline Associated with Pentavalent Antimony: A Randomized Trial for Cutaneous Leishmaniasis.

AbstractCutaneous leishmaniasis (CL) by is associated with decreasing cure rates in Brazil. Standard treatment with pentavalent antimony (Sb) cures only 50-60% of the cases. The immunopathogenesis of CL ulcer is associated with high interferon-γ and tumor necrosis factor (TNF) production.

Atypical Manifestations of Cutaneous Leishmaniasis in a Region Endemic for Leishmania braziliensis: Clinical, Immunological and Parasitological Aspects.

Background: Atypical cutaneous leishmaniasis (ACL) has become progressively more frequent in Corte de Pedra, Northeast Brazil. Herein we characterize clinical presentation, antimony response, cytokine production and parasite strains prevailing in ACL.

Methodology/principal Findings: Between 2005 and 2012, 51 ACL (cases) and 51 temporally matched cutaneous leishmaniasis (CL) subjects (controls) were enrolled and followed over time in Corte de Pedra.

The gp63 Gene Cluster Is Highly Polymorphic in Natural Leishmania (Viannia) braziliensis Populations, but Functional Sites Are Conserved.

GP63 or leishmanolysin is the major surface protease of Leishmania spp. involved in parasite virulence and host cell interaction. As such, GP63 is a potential target of eventual vaccines against these protozoa.

Insulin-like growth factor-I serum levels and their biological effects on Leishmania isolates from different clinical forms of American tegumentary leishmaniasis.

Background: American tegumentary leishmaniasis (ATL) in Brazil is mostly caused by Leishmania (Viannia) braziliensis, with known forms of the disease being cutaneous (CL), mucosal (ML) and disseminated (DL) leishmaniasis. The development of the lesion in ATL is related both to the persistence of the Leishmania in the skin and to the parasite-triggered immune and inflammatory responses that ensue lesions. In this context one factor with expected role in the pathogenesis is insulin-like growth factor (IGF)-I with known effects on parasite growth and healing and inflammatory processes.

Immunologic Markers of Protection in Leishmania (Viannia) braziliensis Infection: A 5-Year Cohort Study.

Background: The control of Leishmania braziliensis by individuals with subclinical infection (SC) are unknown.

Methods: A cohort of 308 household contacts (HCs) of patients with cutaneous leishmaniasis (CL) was established in 2010 in an endemic area and followed up for 5 years. Whole-blood cultures stimulated with soluble Leishmania antigen and a Leishmania skin test (LST) were performed in years 0, 2, and 4.

Wound healing genes and susceptibility to cutaneous leishmaniasis in Brazil: role of COL1A1.

Previous studies have demonstrated a role for wound healing genes in resolution of cutaneous lesions caused by Leishmania spp. in both mice and humans, including the gene FLI1 encoding Friend leukemia virus integration 1. Reduction of Fli1 expression in mice has been shown to result in up-regulation of collagen type I alpha 1 (Col1a1) and alpha 2 (Col1a2) genes and, conversely, in down-regulation of the matrix metalloproteinase 1 (Mmp1) gene, suggesting that Fli1 suppression is involved in activation of the profibrotic gene program.

Comparative analysis of the tissue inflammatory response in human cutaneous and disseminated leishmaniasis.

Cutaneous leishmaniasis (CL) is the most frequent clinical form of tegumentary leishmaniasis and is characterised by a single or a few ulcerated skin lesions that may disseminate into multiple ulcers and papules, which characterise disseminated leishmaniasis (DL). In this study, cells were quantified using immunohistochemistry and haematoxylin and eosin staining (CD4+, CD68+, CD20+, plasma cells and neutrophils) and histopathology was used to determine the level of inflammation in biopsies from patients with early CL, late CL and DL (ulcers and papules). The histopathology showed differences in the epidermis between the papules and ulcers from DL.

Inflammation in disseminated lesions: an analysis of CD4+, CD20+, CD68+, CD31+ and vW+ cells in non-ulcerated lesions of disseminated leishmaniasis.

Disseminated leishmaniasis (DL) differs from other clinical forms of the disease due to the presence of many non-ulcerated lesions (papules and nodules) in non-contiguous areas of the body. We describe the histopathology of DL non-ulcerated lesions and the presence of CD4-, CD20-, CD68-, CD31- and von Willebrand factor (vW)-positive cells in the inflamed area. We analysed eighteen biopsies from non-ulcerated lesions and quantified the inflamed areas and the expression of CD4, CD20, CD68, CD31 and vW using Image-Pro software (Media Cybernetics).

Association between an emerging disseminated form of leishmaniasis and Leishmania (Viannia) braziliensis strain polymorphisms.

Leishmania (Viannia) braziliensis causes three main types of American tegumentary leishmaniasis (ATL), localized cutaneous leishmaniasis (CL), mucosal leishmaniasis (ML), and disseminated leishmaniasis (DL). All forms are observed among individuals of Corte de Pedra, Brazil. We previously used random amplified markers to identify a multiclonal population among L.

A proposed new clinical staging system for patients with mucosal leishmaniasis.

Mucosal leishmaniasis (ML) occurs mainly in areas where Leishmania braziliensis is transmitted. It affects predominantly the nasal mucosa and, in more severe forms, can lead to significant tissue destruction. There is no standard method for grading the severity of disease.

Wound healing genes and susceptibility to cutaneous leishmaniasis in Brazil.

Leishmania braziliensis causes cutaneous (CL) and mucosal (ML) leishmaniasis. In the mouse, Fli1 was identified as a gene influencing enhanced wound healing and resistance to CL caused by Leishmania major. Polymorphism at FLI1 is associated with CL caused by L.

Immunoregulatory and Effector Activities in Human Cutaneous and Mucosal Leishmaniasis: Understanding Mechanisms of Pathology.

Individuals infected with may develop the relatively benign localized cutaneous (CL) form or the mucosal (ML) form of the disease, which represents a more severe and mutilating variation. Interaction between parasite and host cells, as well as the genetic background of the host, are important determinants of the immune response, which is critical in determining disease outcome. Our studies over the years have been designed to determine the immunoregulatory and effector functions that culminate in the formation of lesions in CL and ML disease and how these host response factors may be better understood for design of novel therapies and prophylaxis.

The -2518bp promoter polymorphism at CCL2/MCP1 influences susceptibility to mucosal but not localized cutaneous leishmaniasis in Brazil.

Mucosal leishmaniasis (ML) follows localized cutaneous leishmaniasis (CL) caused by Leishmania braziliensis. Proinflammatory responses mediate CL self-healing but are exaggerated in ML. Proinflammatory monocyte chemoattractant protein 1 (MCP-1; encoded by CCL2) is associated with CL.

CXCR1 and SLC11A1 polymorphisms affect susceptibility to cutaneous leishmaniasis in Brazil: a case-control and family-based study.

Background: L. braziliensis causes cutaneous (CL) and mucosal (ML) leishmaniasis. Wound healing neutrophil (PMN) and macrophage responses made following the bite of the vector sand fly contribute to disease progression in mice.

Influence of helminth infections on the clinical course of and immune response to Leishmania braziliensis cutaneous leishmaniasis.

Background: Helminth infections influence the clinical outcome of and immune response to certain immune-mediated diseases.

Methods: We conducted a cohort study of 120 patients to examine the role that intestinal helminth infection plays in the clinical course of and immune response to cutaneous leishmaniasis (CL) treated with pentavalent antimony.

Results: Patients coinfected with Leishmania braziliensis and helminths took longer to heal (relative hazard for healing, 0.